Group II Metabotropic Glutamate Receptors as Potential Pharmaceutical Targets for Neurofibroma Formation

摘要

Neurofibroma formation might require PI3K hyperactivation within the glial layer that surrounds motor neurons, and yet the signals regulating PI3K remain incompletely understood. We hypothesized that activation of the metabotropic glutamate receptor DmGluRA might activate PI3K in glia. In task No. 1, we proposed to test if inhibition of DmGluRA-PI3K activity in motor neurons is sufficient to activate PI3K in the analogue of the Schwann cell called the peripheral glia (as monitored by perineurial glial growth). We found that inhibiting PI3K activity by introducing the DmGluRA112b null mutation, or by expressing the PTEN or Foxotransgenes in motor neurons did significantly increase perineurial glial growth, which supports the hypothesis. In task No. 2, we proposed to determine if DmGluRA activity in peripheral glia is required for PI3K activation. We found that inhibiting DmGluRA activity partly, but not completely, suppressed genotypes that increase perineurial glial growth, suggesting that DmGluRA as well as another neurotransmitter receptor regulate PI3K activity.